Comparative effects of simvastatin (MK-733) and pravastatin (CS-514) on hypercholesterolemia induced by cholesterol feeding in rabbits.

The preventive effects of simvastatin (MK-733) and pravastatin (CS-514), 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors, on hypercholesterolemia induced by 0.25% cholesterol feeding were compared in rabbits. MK-733 (6, 2 and 0.7 mg/kg) was found to prevent the increase in serum total cholesterol levels dose-dependently. High dose CS-514 (18 mg/kg) also limited the increase in the cholesterol levels, but medium (6 mg/kg) and low doses (2 mg/kg) of CS-514 were ineffective in preventing it. MK-733 inhibited the increase in VLDL and LDL cholesterol levels dose-dependently. MK-733 suppressed the increase in serum phospholipid levels. MK-733 inhibited the accumulation of cholesterol in the liver. The high dose of CS-514 also limited it. High dose MK-733 (6 mg/kg) reduced the cholesterol concentration in gallbladder bile. Neither MK-733 nor CS-514 affected bile acid excretion in the gallbladder bile. High dose MK-733 decreased the lithogenic index. MK-733 increased the number of LDL receptors, and high dose CS-514 also increased it. The suppressive effect of CS-514 on serum cholesterol levels at 18 mg/kg was found to be less than that of MK-733 at 0.7 mg/kg.